Chang Li-Yun, Liu Li-Yu D, Roth Don A, Kuo Wen-Hung, Hwa Hsiao-Lin, Chang King-Jen, Hsieh Fon-Jou
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Biometry Division, Department of Agronomy, National Taiwan University, Taipei 106, Taiwan.
Int J Genomics. 2015;2015:403576. doi: 10.1155/2015/403576. Epub 2015 Aug 23.
Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(-) and ER(-)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(-) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature.
背景。分析181例乳腺癌样本的基因表达谱，以基于核受体NR5A1和NR5A2相关的转录网络确定其预后特征。方法。采用监督网络分析方法构建NR5A介导的转录调控网络。利用其他生物信息学工具和统计方法来确认和扩展网络分析方法的结果。结果。在雌激素受体阴性（ER(-)）和ER(-)/ER(+)混合队列中，NR5A2表达均为乳腺癌预后的负性因素。NR5A2介导的转录活性的临床和队列意义表明，它可能在减弱分级进展和癌症相关信号转导途径中起重要作用。基于15个不同探针的结果确定了预示预后不良的NR5A2特征。另外，当NR5A2同时低表达时，NR5A1的表达预示良好预后。还确定了由NR5A1介导的8个转录因子的良好特征。结论。通过NR5A2介导的15基因特征确定了预后不良与NR5A2活性的相关性。NR5A2可能是治疗各乳腺癌亚型中一部分乳腺癌肿瘤，尤其是ER(-)乳腺癌肿瘤的潜在药物靶点。由NR5A1介导的8基因特征预示了NR5A1的良好预后特征。
